In the United States alone, approximately 500,000 deaths will result from rupture of plaques considered "insignificant" on an angiographic evaluation. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. Therefore, there is a definite and urgent clinical need for an imaging technique that can identify and characterize the vulnerability of atherosclerotic plaques during coronary artery interventions. The overall goal of our research program is to develop an in-vivo imaging technology - intravascular photoacoustic imaging - capable of visualizing both structural and functional properties of atherosclerotic plaques. The underlying hypothesis of this project is that intravascular photoacoustic (IVPA) imaging combined with intravascular ultrasound (IVUS) imaging is possible and can be used to distinguish vulnerable plaques, thus assisting pre-intervention planning, the intervention itself, and improving the post-intervention outcome. Most importantly, the proposed photoacoustic imaging will not significantly change the current protocol of coronary artery intervention. A wide range of technical, scientific and clinical problems must be addressed to fully explore the capabilities of intravascular photoacoustic imaging in interventional cardiology. The central theme of the current project is to address the areas of known technical concerns so that the broader developmental efforts may proceed with minimal risk. The main objective of this R21 application is, therefore, to develop and initially test a prototype of the photoacoustic imaging system for intravascular applications. To achieve our objective, we will first design and build the intravascular photoacoustic imaging system based on a mechanically scanned, single element transducer IVUS cathetrer interfaced with a tunable laser source. We will also develop both theoretical and numerical foundations for photoacoustic and ultrasound imaging to optimize the performance of the system. Second, we will test the developed imaging system using tissue mimicking phantoms. Third, the developed imaging system will be tested using animal tissue samples where ultrasonic and photoacoustic images will be correlated with histological slides and biochemical analysis of tissue. Finally, based on the insights gathered during the project, we will outline the design and technical specifications of an intravascular photoacoustic imaging system. Atherosclerotic cardiovascular disease results in more than 19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs - in the United States alone, approximately 500,000 deaths per year will result from rupture of plaques considered "insignificant" on an angiographic evaluation. Therefore, there is a definite and urgent clinical need for an imaging technique that can identify and characterize the vulnerability of atherosclerotic plaques during coronary artery interventions including percutaneous balloon angioplasty, endovascular stenting, ablation/vaporization and brachytherapy. [unreadable] [unreadable] [unreadable]